70 PART 2 Examining Tools and Processes

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» ^{Drug description: This description details each drug that will be administered}

to the participants. This includes the chemical composition with the results of

chemical analysis of the drug, if available. It also includes instructions about

how to store, prepare, and administer the drug correctly.»

» ^{Blinding and randomization schemes: These schemes include descriptions}

of how and when the study will be unblinded. This includes the emergency

unblinding of individual participants if necessary. See the earlier section

“Using randomization” for more information.»

» ^{Procedural descriptions: This section describes every procedure that will}

be performed at every visit. These include administrative procedures, such

as enrollment and informed consent, and diagnostic procedures, such as

physical exams and measuring vital signs. It covers all activities where

data are collected from participants in the study.»

» ^{Safety considerations: These factors include the known and potential side}

effects of each drug included. This section also includes the known and

potential side effects of each procedure in the study, including X-rays, MRI

scans, and blood draws. It also describes steps taken to minimize the risk to

the participants.»

» ^{Handling of adverse events: This section describes how adverse events will}

be addressed should they occur during the study. It includes a description of

the data that will be recorded, including the nature of the adverse event,

severity, dates and times of onset and resolution, any medical treatment given

for the event, and whether or not the investigator thinks the event was related

to the study drug. It also explains how the research study will support the

participant after the adverse event.»

» ^{Definition of safety, efficacy, and other analytical populations: This}

section includes definitions of safety and efficacy variables and endpoints. In

other words, this section defines variables or changes in variables that serve

as indicators of safety or efficacy.»

» ^{Planned enrollment and analyzable sample size: Justification for these}

numbers must also be provided.»

» ^{Proposed statistical analyses: Some protocols describe, in detail, every}

analysis for every objective. Others include only a summary and refer to a

separate Statistical Analysis Plan (SAP) document for details of the proposed

analysis. This section should also include descriptions of how missing data will

be handled analytically, adjustments for multiple testing to control Type I errors

(see Chapter 3), and whether any interim analyses are planned. If a separate

SAP is used, it typically contains a detailed description of all the calculations and

analyses that will be carried out on the data, including the descriptive summa-

ries of all data and the testing of all the hypotheses specified in the protocol.

The SAP also usually contains mock-ups called shells of all the tables, listings,

and figures (referred to as TLFs) that will be generated from the data.